Method for the manufacture of filter wells

ABSTRACT

A filter well of plastic having a bottom portion with an outlet and supporting a filter provided on top of the outlet, which filter is well sealed against leakage of liquid, is produced by first forming a bottom portion having a supporting surface for the filter and an outlet opening. Thereafter, a filter is applied on the bottom portion so that it covers at least essentially the whole bottom portion. Then, the cylindrical wall portion of the filter well is formed against the bottom portion with the lower part of the wall portion surrounding the edge of the filter and the upper edge of the bottom portion so that the bottom and wall portions form a fused unit with the outer edge of the filter being fused into the filter well material.

The present invention relates to the production of filter wells usefulfor separating a solid phase from a liquid.

Separating a solid phase from a solution is a common process in abiotechnological laboratory and is carried out mainly either bycentrifugation or by collecting the solid phase on a filter. Asexamples, the preparation of nucleic acids from bacteria,bacteriophages, DNA-synthesis, PCR products, etc., can be mentioned.Normally, such filtering is carried out in so called filter wells, i.e.a small tube or the like containing a filter through which the liquidphase is forced by applying vacuum on the underside of the filter orpressure on the upside of the filter. A device for carrying outbiochemical reactions in microtitre plates, where a solution is forcedthrough filter wells by means of gas pressure, is described in our U.S.Pat. No. 5,273,718. Relative to the application of vacuum, the use of apositive pressure on the upside of the filter has i.a. the advantagesthat the solid phase as well as the liquid phase easily can be collectedand that a greater pressure difference between the upside and theunderside of the filter is possible (greater than 1 bar) but requires onthe other hand a very good sealing between the filter and the wall ofthe filter well in order to avoid a leakage of liquid past the filter.

A method of providing the necessary sealing upon filtering by means ofvacuum is described in WO 86/07606, where a test plate of microtitrewell type is produced in that a filter membrane is placed between anupper part and lower part which are then pressed together so that anumber of wells provided with filters, are formed. The sealing betweenthe wells is secured in that the upper and lower parts between the wellportions are provided with matching ridges and recesses so that thefilter membrane breaks upon pressing the parts together when a ridge isforced into the corresponding recess. The upper and lower parts are thenfused together in these portions by means of heat, e.g. by use ofultrasound. However, this method is limited to a microtitre well formatwith fixed wells.

Systems based on separate filter wells offer greater flexibility.Holders can i.a. be supplied for a varying number of filter wells of oneand the same type. However, for this case, no sealing method which issufficient in all respects has been described so far. Thus, at leastunder certain conditions, fixing the filter in the well by glueingcauses release of contaminating substances to the passing liquid.Ultrasound welding as in the above WO 86/07606, has turned out todestroy the filter. A sealing arrangement of O-ring type is possible perse but results in a construction which for most purposes is toocomplicated and thereby expensive.

EP-A-328 038 describes the production of a filter well by injectionmoulding of the filter well in one piece and at the same time castingthe filter edge integral with the wall of the well. This method has i.a.the disadvantage that it does not allow the forming of any supportsurface for the filter. Moreover, the filter is compressed during theforming process which can cause damages to the active filtering surfaceof the filter. Furthermore, in the method as specifically described,only one side of the filter is fixed in the wall of the filter well.

U.S. Pat. No. 4,113,627 describes the production of a filter forinfusion liquids where two preformed filter housing halves with a filterclamped therebetween, are sealed at the outer edge by injection mouldingof a thermoplastic resin. Besides the fact that the manufacturingprocess is relatively complicated, the clamping of the filter betweenthe housing parts can damage the filter surface. Moreover, only one sideof the filter is cast integral with the thermoplastic resin.

The present invention relates to a method of producing separate filterwells, which does not exhibit the disadavantages and inconveniencesmentioned above at the same time as it in combination with a simpleprocedure secures an extraordinary sealing of the edge of the filter orthe membrane so that there is no risk of any leakage past the filterwhen a positive pressure is applied to the upside of the filter.Moreover, the filter well gives support to the filter at high pressures.

Similar to the method according to the above mentioned EP-A-328 038, theinvention is based upon the idea of producing the filter well by formingof plastic and at the same time fix the filter in the filter well.However, according to the invention, the filter is fixed in that thefilter edge is double-sidedly embedded or fused into the wall of thewell during the actual forming process at the same time as the filter issupported by a bottom portion formed in advance and having a supportingsurface for the filter.

More in detail, the filter well is produced by first forming a bottomportion provided with a supporting surface for the filter and apreferably central outlet opening for freely dripping liquid.Thereafter, a filter (or membrane) is applied on the supporting surfaceof the bottom portion so that the filter at least essentially covers thewhole bottom portion. Finally, the cylindrical wall portion of thefilter well is formed against the bottom portion with the lower part ofthe wall portion surrounding the edge of the filter and the upper edgeof the bottom portion so that the bottom and wall portions form a fusedunit, the outer edge of the filter being fused into the filter wellmaterial.

Preferably, the supporting surface extends inside the inner side of thecylinder wall so that it supports at least part of the active filteringsurface of the filter.

Preferably, the filter is somewhat larger than the bottom portion sothat the filter, before the forming of the cylindrical wall portion,extends beyond the periphery of the bottom portion.

According to a preferred embodiment, the bottom portion is produced witha fine flow channel pattern in the supporting surface, which results invery small losses upon recovery of the liquid phase.

A device for producing the filter well, thus, has means for forming thebottom portion, means for applying a filter on the bottom portion, andmeans for forming the wall portion of the filter well against the bottomportion. Such a device can advantageously be in the form of a singlemoulding tool with several stations.

Injection moulding is a preferred forming method.

Preferably, the wall portion and the bottom portion of the filter wellare produced from the same material, particularly a thermoplastic resin.

An embodiment of the method according to the invention will be describedmore in detail below with reference to the appended drawings on which

FIGS. 1-7 are cross-sectional views of parts of an injection mouldingtool at different stages of the manufacturing of a filter well accordingto the invention,

FIG. 8 is a cross-sectional view of the finished filter well,

FIG. 9 is a section along the line A--A in FIG. 8 with the filter partlybroken away and

FIG. 10 is a schematical, exploded view of an injection moulding toolcomprising the tool parts of FIGS. 1-7.

The tool parts illustrated in FIGS. 1-7 are included in an integratedtool for carrying out all steps in the production of the filter well.The tool which for reasons of clarity is not shown in its whole, has astationary part shown uppermost in the Figures and, therefore,henceforth called upper part, and a movable, lower part in the Figures,henceforth called lower part which by rotation in the horizontaldirection can be moved to different stations of the upper part.

FIG. 1 shows the tool portion for injection moulding of the bottomportion of the filter well. The portion that is included in theabove-mentioned upper, stationary tool part is denoted 1 and the portionthat is included in the movable lower part is denoted 2. The two parts 1and 2 are horizontally displaceable relative to each other, e.g. byrotation, in a partition plane 3 when the lower part 2 of the tool hasbeen moved away from the upper part 1. (The same reference numerals forthe upper and lower tool part, respectively, are used throughout theother Figures.)

The upper tool part 1 has a cylindrical, upper mould element 4 having acentral, threaded boring 5 which abrubtly changes into a boring 6 with asmaller diameter. The latter extends in its turn up to the lower end 7of the mould element. A pin 8 adapted to the borings 5, 6 is screwedinto the boring 5 and has a needle portion 9 which extends below themould element end 7. A pattern of elongated ridges 10 which run radiallyand, possibly, also in the transverse direction, e.g. annularly,starting a distance inside the edge and up to the bore 6, are formed inthe end 7 for forming flow channels in the bottom of the filter well. Amethod for forming, by etching, a fine pattern of ridges which are toform a corresponding fine pattern of flow channels in the filter well,is described in our PCT-application PCT/SE95/00141 filed on Feb. 10,1995 entitled, "Filter well and a method for its manufacture", of evendate and based on the Swedish patent application No. 9400437-1 (thecontents of which is incorporated herein by reference).

A matching, cylindrical, lower mould element 11 is verticallydisplaceable in the lower tool part 2 right in front of the mouldelement 4. Together with the end 7 of the mould element 4 and theuppermost part of the adjacent main portion of the lower tool part 2,the upper part 12 of this mould element 11 is designed to delimit amould cavity 13 for forming the bottom portion of the filter well. Apointed depression 14 into which the needle portion 9 of the mouldelement 4 extends, ends in a central boring 15 in the mould element 11.For reasons that will be apparent further below, the boring 15 isconnectable to a vacuum source.

In FIG. 1, the mould cavity 13 is shown filled with the desiredinjection moulding material, e.g. polypropylene, injected via an openingwhich is not shown in this connection for reasons of clarity. In thecase shown, the finished bottom portion 16 has a drop tip 17 whichencloses a central opening 18, and a peripheral collar portion 19.Moreover, on the upside it has a system of flow channels 20 formed bythe above-mentioned ridges 10 in the end 7 of the mould element 4, andwhich extend radially from an unpatterned rim portion 21 to the opening18. Also, there may be connections between the radial channels, e.g. inthe form of annular channels which are concentric with the opening 18 inthe bottom portion 16.

After injection moulding of the bottom portion 16, vacuum is applied tothe central boring 15 of the lower mould element 11, so that the bottomportion 16 stays on the mould element when the tool opens up along thepartition plane 3, i.e. the lower, movable tool part 2 is displaceddownwards in the Figure. At the same time, the lower mould element 11 isalso raised somewhat relative to the tool part 2 so that the side edgeof the bottom portion 16 loosens from the adjacent portion of the lowertool part 2. The lower part 2 of the injection moulding tool is thenswung so that the bottom portion 16 which is still kept on the lowermould element 11 is brought to a filter application station illustratedin FIG. 2, in the upper tool part 1.

In this filter application station the lower mould element 11 is swungright in front of a vertical punch 22 which runs in a hole 23 in thetool part 1. A central boring 24 in the punch 22 can be connected to asource of compressed air/vacuum and ends in e.g. a cross- or star-shapedend recess 25.

The punch 22 is adapted to punch out a filter disc from a filter sheetor strip 26, e.g. a so called sterile filter or a membrane of polyamidewith fine pores, a polypropylene filter or a glass fibre filter, whichis fed over the punch hole 23 via a horizontal gap 27 in the upper toolpart. In FIG. 2, the punch 22 has punched out a filter disc 28 which iskept against the punch via vacuum connected to the boring 24 in thecenter of the punch. Just before the punch end with the filter 28contacts the bottom portion 16, the vacuum is changed into positivepressure so that the filter is pressed against the bottom portion 16 andthe filter is thereafter kept against the bottom portion via the vacuumconnected earlier to the boring 15, which in this station reaches thefilter through the central opening 18 in the bottom portion.

Thereafter, the punch 22 is lifted up and the lower tool part 2 is swungto a further station of the upper tool part 1 for injection moulding ofthe cylindrical wall portion of the filter well. In FIG. 3, the portionin question of the lower tool part is shown on its way to this injectionmoulding station. The vacuum in the boring 15 is still applied so thatthe filter 28 all the time is kept against the bottom portion 16 of thefilter well.

FIG. 4 shows the lower tool part with the bottom portion 16 injectionmoulded earlier still in place at the next injection moulding station.The upper tool part has here two portions arranged on top of each otherand being movable relative to each other, of which the lower toolportion 29 delimits a cavity 30 which can be opened and which isarranged right before the injection moulded bottom portion 16, while theupper tool portion 31 has a boring 32 aligned with the cavity 30, whichslidably receives a vertical, cylindrical element 33. The latter extendswith its lower part into the cavity 30 to form a mould core. Togetherwith the wall of the cavity 30, the lower edge of the tool portion 31,the upper part of the lower tool portion 2 and the already injectionmoulded bottom portion 16, this mould core delimits a mould cavity 34for injection moulding of the cylindrical wall portion of the filterwell. As apparent from FIG. 4, the bottom portion 16 is somewhatelevated above the lower tool part 2 for the mould cavity to extendbeyond and surround the upper edge of the bottom portion 16. Aneffective sealing between the cylindrical core 33 and the injectionmoulded bottom portion 16 is secured in that the filter 28 is clampedagainst the unpatterned (i.e. without any flow channels) rim portion 21of the bottom portion 16 via a corresponding, vertically extending rimportion 35 at the end of the cylindrical core 33. The outermost portionof the filter 28 and the underlying portion of the already injectionmoulded bottom portion 16 are, however, not covered by the cylindricalcore 33 but, as apparent from the Figure, extend into the mould cavity34.

A plastic melt, e.g. polypropylene, is now injected under high pressureinto the mould cavity 34 as shown in FIG. 5 via an opening (not shown)in order to form the cylindrical portion 36 of the filter well. Asapparent from FIG. 5, the melt surrounds the upper edge of the bottomportion 16 and extends a distance over the filter 28 so that this isembedded or moulded into the cylindrical wall. Upon solidification ofthe melt, the injection moulded cylindrical portion 36 tends to contractrelative to the bottom portion 16 injection moulded earlier, which leadsto that it compresses the embedded filter edge resulting in anextraordinary sealing against the filter.

Upon solidification of the melt, it has combined itself with the bottomportion 16 into an integrated unit with the outer portion of the filter28 melted into the same as apparent from FIG. 6 which shows the finishedfilter well 37 kept on the cylindrical core 33 but with the tool portion29 in FIG. 5 opened.

The filter well 37 is then pushed off the cylindrical core 33 by adownwards directed movement of the tool portion 31 as illustrated inFIG. 7.

In FIG. 8, the finished well 37 is shown removed from the injectionmoulding tool with the filter melted into the same. Thus, the filterwell 37 comprises the bottom and cylindrical portions 16, 36 meltedtogether into one piece with the filter 28 supported on the well bottomwhich is provided with flow channels 20 and which forms a supportingsurface 16a for the filter, wherein a peripheral portion of both sidesof the filter is properly melted or fused into the cylindrical portion.This fusion of the filter ensures a very effective and safe sealing andconsequently there is no risk of any leakage of liquid past the filterwhen liquid is pressed through the bottom opening 18 via the filter 28.

An example of how the flow channel pattern may look is illustrated inFIG. 9. Besides the radial channels 20 which extend radially to theoutlet opening 18, a number of flow-equalizing cross-channels 38 arealso provided, which extend concentrically with the opening 18. Thechannels 20, 38 as well as the intermediate ridge portions (i.e. thefilter supporting portions) 39, preferably have a very small width, e.g.of the order of 0.1 mm. As already mentioned, this leads to that theremaining liquid volume in the filter tube after the filtering will bevery small and that the contact surfaces with the filter are minimizedso that essentially all of the filter surface is active upon filtration.

FIG. 10 illustrates schematically how the earlier mentioned integratedinjection moulding tool with the tool stations shown in FIGS. 1-7 can bearranged in an injection moulding machine. It should be noted that whilein FIGS. 1-7 the respective tool portions are shown with the stationarytool part 1 at the top and the movable tool part 2 below, these two toolparts are arranged horizontally as in FIG. 10. Thus, the stationary toolpart 1 is located to the left in the Figure, while the movable tool part2 is located to the right.

The stationary tool part 1 has a first station 40, corresponding to thetool portion illustrated in FIG. 1, for injection moulding of the bottomportion of the filter well, a second station 41, corresponding to thetool portion in FIG. 2, for punching and applying the filter onto thebottom portion, and a third station 42, corresponding to the toolportion in FIGS. 4-7, for injection moulding of the cylindrical portionof the filter well.

The movable tool part which is laterally displaceable, has a rotatableelement 43 with four identical tool portions 44-47 at the sameperipheral distance from each other as the distance between the stations40-42 in the stationary tool part. Three of the portions 44-47 are ateach processing instance in active engagement with the stations 40-42 inthe stationary tool half 1. With the movable tool part 2 pushed againstthe stationary tool part 1, thus, injection moulding of the bottomportion at the tool portion 44, application of a filter onto an alreadyinjection moulded bottom portion at the tool portion 45, and injectionmoulding of the cylindrical portion onto a bottom portion provided witha filter at the tool portion 46, take place at the same time.Thereafter, the two tool halves 1, 2 are brought apart and the rotatableelement 43 is rotated 90°. A bottom portion is now injection moulded at47, a filter is applied to the bottom portion at 44 and a cylindricalportion is injected moulded at 46, etc.

The capacity of the tool may, if so desired, be increased in that eachstation 40, 41 and 42 is provided with several sets, e.g. four sets, ofthe tool parts included in each station and in that each tool portion44-47 is provided with as many, e.g. four, sets of these tool partsright before the respective station 40, 41 and 42.

The invention is of course not restricted to just the embodimentdescribed above and shown on the drawings, but many variations andmodifications may be made without departing from the general inventiveidea as it is defined in the appended claims.

I claim:
 1. A method of producing a plastic filter well having a cavitydefined by a bottom portion with an outlet and an upper part of acylindrical wall portion extending upwardly from the bottom portion,said bottom portion supporting a filter provided on top of said outletcomprising:(i) forming the bottom portion having a supporting surfacefor the filter and an outlet opening; (ii) applying the filter on thebottom portion so that the filter at least essentially covers the wholebottom portion; and (iii) the forming the cylindrical wall portionhaving the upper part and a lower part, wherein the upper part of thecylindrical wall portion surrounds the cavity and the lower part of thecylindrical wall connects to said filter on said bottom portion, withthe lower part of the cylindrical wall portion surrounding an outer edgeof the filter and an upper edge of the bottom portion so that the bottomportion and the lower part of the cylindrical wall portion form a fusedunit, the outer edge of the filter being fused into the lower part ofthe cylindrical wall portion of the plastic filter well.
 2. The methodaccording to claim 1, wherein the forming of the bottom portion andforming of the cylindrical wall portion of the filter well are carriedout by injection moulding.
 3. The method according to claim 1, whereinthe bottom portion and the cylindrical wall portion are formed from thesame material.
 4. The method according to claim 1, wherein duringforming of the cylindrical wall portion, the filter inside an edgeportion that is to be fused is pressed against a rim portion of anupside of the bottom portion.
 5. The method according to claim 1,wherein an upside of the bottom portion is formed with radial flowchannels which run towards the outlet opening, and, optionally, alsoflow channels which are concentric with the outlet opening and whichmutually connect the radial flow channels, ridge portions between theflow channels supporting the filter.
 6. The method according to claim 1,wherein step (ii) further comprises punching the filter from a filterblank.
 7. The method according to claim 1, wherein the filter in step(ii) extends beyond a periphery of the bottom portion.
 8. The methodaccording to claim 1, wherein a supporting surface of the bottom portionfor the filter extends inside an inner side of the cylindrical wall tosupport at least part of an active filtering surface of the filter. 9.The method according to claim 1, wherein the outlet opening is centrallylocated in the bottom portion.